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. 2020 Aug 17;6(3):00049-2020.
doi: 10.1183/23120541.00049-2020. eCollection 2020 Jul.

Physiological signature of late-onset nonallergic asthma of obesity

Anne E Dixon  1 , Ubong Peters  1 , Ryan Walsh  2 , Nirav Daphtary  1 , Erick S MacLean  1 , Kevin Hodgdon  1 , David A Kaminsky  1 , Jason H T Bates  1
Affiliations

Physiological signature of late-onset nonallergic asthma of obesity

Anne E Dixon et al. ERJ Open Res. .

Abstract

Introduction: Obesity can lead to a late-onset nonallergic (LONA) form of asthma for reasons that are not understood. We sought to determine whether this form of asthma is characterised by any unique physiological features.

Methods: Spirometry, body plethysmography, multiple breath nitrogen washout (MBNW) and methacholine challenge were performed in four subject groups: Lean Control (n=11), Lean Asthma (n=11), Obese Control (n=11) and LONA Obese Asthma (n=10). The MBNW data were fitted with a novel computational model that estimates functional residual capacity (FRC), dead space volume (VD), the coefficient of variation of regional specific ventilation (CV,V'E) and a measure of structural asymmetry at the level of the acinus (sacin).

Results: Body mass index and waist circumference values were similar in both obese groups, and significantly greater than in lean asthmatic individuals and controls. Forced vital capacity was significantly lower in the LONA Asthma group compared with the other groups (p<0.001). Both asthma groups exhibited similar hyperresponsiveness to methacholine. FRC was reduced in the Obese LONA Asthma group as measured by MBNW, but not in obese controls, whereas FRC was reduced in both obese groups as measured by plethysmography. VD, CV,V'E and sacin were not different between groups.

Conclusions: Chronic lung compression characterises all obese subjects, as reflected by reduced plethysmographic FRC. Obese LONA asthma is characterised by a reduced ability to recruit closed lung units, as seen by reduced MBNW FRC, and an increased tendency for airway closure as seen by a reduced forced vital capacity.

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Conflict of interest statement

Conflict of interest: A.E. Dixon reports that MitoQ supplied the study drug for a clinical trial outside the submitted work. Conflict of interest: U. Peters has nothing to disclose. Conflict of interest: R. Walsh has nothing to disclose. Conflict of interest: N. Daphtary has nothing to disclose. Conflict of interest: E.S. MacLean has nothing to disclose. Conflict of interest: K. Hodgdon has nothing to disclose. Conflict of interest: D.A. Kaminsky reports personal fees from MGC Diagnostics, Inc., for participating as faculty on a course outside the submitted work. Conflict of interest: J.H.T. Bates reports grant R01 HL130847 from the NIH-NHLBI during the conduct of the study. He is a consultant for an minor shareholder in Oscillavent, LLC (Iowa), and a consultant for Healthy Design, LLC (Vermont), outside the submitted work. In addition, he has patents (Device and method for lung measurement, US patent application US 20160007882 A1; Variable ventilation as a diagnostic tool for assessing lung mechanical function, PCT Application WO2015127377 A1) pending.

Figures

FIGURE 1
FIGURE 1
Mean values for total lung capacity (TLC), functional residual capacity (FRC) and residual volume (RV) in each of the four study groups, expressed as fractions of 100% predicted TLC for each group as measured by plethysmography. The Lean Control group slightly exceeded 100% predicted TLC. Mean TLC in each of the remaining groups was <100% predicted by amounts that are potentially attributable to volumes of atelectatic (non-recruitable) lung (grey).
FIGURE 2
FIGURE 2
Closed symbols show the parameters derived from multiple breath nitrogen washout pertaining to lung size (a: functional residual capacity (FRC) and b: dead space volume (VD)) for each of the four study groups (means shown as horizontal bars). FRC from nitrogen washout was significantly lower in the late-onset nonallergic (LONA) obese asthma group compared to FRC from nitrogen washout in the other groups (*: ANOVA and paired t-test, p<0.05).
FIGURE 3
FIGURE 3
Parameters derived from multiple breath nitrogen washout pertaining to lung heterogeneity (a: the coefficient of variation of regional specific ventilation CV,V′E and b: a measure of structural asymmetry at the level of the acinus (sacin)) for each of the four study groups (means shown as horizontal bars). There were no significant differences between groups for either parameter.
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